Gastrin - A Potential Predictor of Response to Incretin Therapy in Diabetes Type 2 Patients

Abstract

Background and objectives: Personalized management of diabetes has become an imperative since majority of monotherapy fails within 3 years of its use. Identifying responders from nonresponders for a certain type of therapy would reduce a period of unsuccessful treatment and minimize health care costs. Incretin therapies, mainly glucagon-like peptide (GLP)-1 receptor agonists (GLP- 1RA) are relatively new glucose-lowering agents which increase insulin and lower glucagon response as well as slow down glucose absorption by acting on gastric emptying. However, problem with incretin- based therapy is distinguishing responders from non-responders and currently lack of specific predictors of treatment response.

Discussion: Experimental data demonstrated that activation of GLP-1 and gastrin signaling induces beta cell neogenesis, leading to glucose-dependent insulin secretion. Several studies demonstrated better glycemic control in patients with type 2 diabetes (DMT2) co-treated with proton pump inhibitors (PPI) and incretin based therapy agents.

Conclusion: Higher gastrin levels in patients with diabetes prior to initiation of treatment with incretin mimetics could suggest a better potential for reversible human β-cell reprogramming with concomitant incretin therapy. Therefore, baseline levels of endogenous gastrin could be used as a predictor of response to GLP-1 therapy. In addition, treatment with PPI could also raise gastrin levels and in patients treated with GLP-1RA, lead to better glycemic control by initiating β-cell neogenesis and proliferation of pancreatic β-cells.

Keywords: Diabetes mellitus; GLP-1RA; gastrin; incretin therapy; personalized treatment; β-cell preservation.